Signaling by receptor protein tyrosine kinases (RPTKs) involves the activation of multiple distinct pathways. Grb2 is ubiquitously expressed as a 25 kDa protein that plays a central role in signaling by several receptors (Lowenstein, E. J., et al. (1992) Cell 70:431-442 and Downward, J. (1994) FEBS Letters 338:113-117). It functions as an adaptor protein where its central SH2 domain binds to an autophosphorylation site on the receptor and the two flanking SH3 domains link to effector molecules. One such target is the mammalian homolog of SOS which is a guanine nucleotide exchange factor for ras, so that Grb2 links receptors with the ras pathway. It is now clear that the SH3 domains also link to a variety of other proteins involved in signaling including Vav (Ren, R., et al. (1994) Genes Dev. 8:783-95), c-abl (Ye, Z. S., and Baltimore, D. (1994) Proc. Natl. Acad. Sci. U.S.A. 91:12629-12633), dynamin (Gout, I., et al. (1993) Cell 75:25-36), and SLP-76 (Jackman, J. K., et al. (1995) J. Bio. Chem. 270:7029-7032), but several other binding proteins have been noted during T and B cell signaling (Reif, K. et al. (1994) J. Biol. Chem. 269:14081-14087 and Motto, D. G., et al. (1994) J. Bio. Chem. 269:21608-21613).
There is a need to identify additional proteins involved in tyrosine kinase activation pathways. There is a need to isolate proteins involved in tyrosine kinase activation pathways, and for compositions and methods for producing and isolating proteins involved in tyrosine kinase activation pathways. There is a need to isolated nucleic acid molecules that encode proteins involved in tyrosine kinase activation pathways. There is a need for compounds which modulate the activity of proteins involved in tyrosine kinase activation pathways. There is a need for kits and methods of identifying such compounds.